title: Bioavailability of testosterone enanthate dependent on genetic variation in the phosphodiesterase 7B but not on the uridine 5'-diphospho-glucuronosyltransferase (UGT2B17) gene.
abstract: OBJECTIVE
  To study the disposition of serum testosterone and seven of its metabolites before and after 2 days of an intramuscular dose (500 mg) of testosterone enanthate in relation to the phosphodiesterase (PDE7B) and the uridine 5'-diphospho-glucuronosyltransferase (UGT2B17) genotypes.
  
  
  METHODS
  Patients were genotyped for UGT2B17 deletion polymorphism and single nucleotide polymorphisms in the PDE7B gene. The involvement of PDE7B in hydrolysis of enanthate was assessed in human liver homogenates.
  
  
  RESULTS
  Genetic variation in the PDE7B gene was found to be associated with the serum level of testosterone. Individuals homozygous for PDE7B rs7774640 G allele had a smaller increase (2.5-fold) in the serum testosterone levels compared with carriers of the A allele (3.9-fold, P=0.0006). In addition, genetic variation in the PDE7B gene significantly influences the testosterone/epitestosterone ratio, a biomarker of testosterone doping. Our in-vitro incubation studies confirmed that PDE7B serves as a catalyst of the hydrolysis of testosterone enanthate. The UGT2B17 deletion polymorphism did not show any significant association with serum testosterone levels or the other androgen metabolites investigated.
  
  
  CONCLUSIONS
  We have shown that PDE7B is involved in the hydrolysis of testosterone enanthate and that genetic variation in the PDE7B gene is a determinant of the systemic levels of testosterone after administration of testosterone enanthate. It is reasonable to believe that the genetic variation in testosterone bioavailability may be correlated to varying effects of this androgen, whether it is used for replacement therapy or abused in doping. Thus our results may be important to consider in doping test programmes and in therapeutics with androgens and other esterified drugs.
authors.affiliation: Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. ena.ekstrom@ki.se
authors.forename: Lena
authors.initials: L
authors.lastname: Ekström
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Schulze
authors.forename: Chantal
authors.initials: C
authors.lastname: Guillemette
authors.forename: Alain
authors.initials: A
authors.lastname: Belanger
authors.forename: Anders
authors.initials: A
authors.lastname: Rane
mesh_terms: D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000493:pharmacokinetics*; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000235:genetics*; D004845:Epitestosterone / Q000097:blood; D017353:Gene Deletion; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D011110:Polymorphism, Genetic / Q000235:genetics*; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D000728:Androgens; D015778:Minor Histocompatibility Antigens; D013739:Testosterone; D004845:Epitestosterone; C004648:testosterone enanthate; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517463:PDE7B protein, human